Acidosis is one of the most common abnormalities in homeostasis observed in the neonate. However, the renal response of neonates to persistent hypoxia, hypercarbia, and acidosis as seen in respiratory distress syndrome has not been clearly defined. Furthermore, there is reason to believe that the therapeutic modalities currently used may further alter renal function. In order to address these problems we will perform clearance studies in animals rendered either hypoxic, hypercapnic or acidotic alone, or in combination with each other. The renal functional variables to be measured include glomerular filtration rate, renal blood flow, net acid excretion and the clearances of sodium and free water. In addition, the renal function of animals given continuous distending pressure respiratory therapy will be assessed in order to examine its impact. Another form of acidosis, suggested to be associated with a positive hydrogen ion balance, occurs in neonates and young children with conditions known as late metabolic acidosis and distal renal tubular acidosis. The extrarenal mechanisms which may participate in the maintenance of homeostasis in these conditions include hyperventilation, reabsorption of base from the bone and enhanced absorption of potential base by the gastrointestinal tract. The contribution of hyperventilation to homeostasis is limited since the carbon dioxide tension of the blood cannot be lowered much beyond 10 mmHg. Similarly, reabsorption of base from the bone must be limited since these children grow, albeit at a slow rate, and the formation of bone is acidogenic. The contribution of the gastrointestinal tract has not yet been assessed. In order to do this we will perform balance studies in animals rendered chronically acidotic by HCl administration. In addition, we will examine the buffering capacity as well as the histology of the bone. The latter will provide evidence of osteomalacia and hyperparathyroidism. These studies will permit us to make more meaningful therapeutic recommendations for infants with acidosis.